The Vitamin D Newsletter May 2006
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13th Annual Vitamin D Workshop
The Vitamin D Conference just finished in Victoria was nothing short of spectacular. On the bus into Victoria, I met a representative from the National Cancer Institute whose job was simple: her bosses at the NIH wanted to know if they should fund the flood of grant requests about vitamin D. Given the quality of the papers presented, I can't imagine her answer was anything but yes.
Dr. Tony Norman and Dr. Roger Bouillon, the conference organizers, had to choose from over 300 submissions from scientists around the world. The venerable Dr. Bouillon did not try to back off his recent widely quoted warning that more than a billion people in the world are vitamin D deficient.
Both men did a great job balancing presentations on vitamin D nutrition, vitamin D basic science, and the patentable vitamin D analogs sought by drug companies. Of course, I thought more time should have been devoted to vitamin D nutrition but Dr. Norman pointed out that more time was devoted to vitamin D nutrition than ever before. Like Dr. Norman, I am unable to comment on all the presentations that merited it, or this newsletter would be 50 pages long.
Vitamin D's Many Names
It was painful to hear the scientists use 10 different names (interchangeably) for vitamin D, for 25-hydroxy cholecalciferol, and for 1,25-dihydroxy cholecalciferol. Some even called ergocalciferol vitamin D! Can you imagine scientists using the same name for cholesterol, pregnenolone, testosterone, and estradiol? They do exactly that with vitamin D. Editors of the major journals will not accept reasonable names like "vitamin D" for cholecalciferol, "calcidiol" for 25-hydroxy cholecalciferol, and "calcitriol" for 1,25-dihydroxy cholecalciferol. The presentations would have been much smoother if scientists could get together and give vitamin D and its metabolites common names like other steroid hormones.
Dr. Barbara Gilchrest, who fired Dr. Michael Holick from one of his professorships several years ago after Holick wrote a book saying God knew what she was doing when she created sunlight, gave the Plenary Lecture. Wisely, Dr. Gilchrest overwhelmed the audience with graphic pictures of invasive skin cancer to support her argument that sunlight is evil. Of course, it's harder to show pictures of invasive colon cancer, breast cancer, prostate cancer, and the 15 other internal cancers caused by sunlight deprivation.
"Progress Is Impossible Without Change"
However, Dr. Gilchrest is changing her mind. George Bernard Shaw once said, "Progress is impossible without change; and those who cannot change their minds, cannot change anything." Dr. Gilchrest is changing her mind—not about the evils of sunlight—about vitamin D. She is in the process of admitting that this miraculous substance has benefits beyond bone.
Two years ago, she dismissed any concerns about vitamin D with a "take a multivitamin if you are concerned." Now she believes the Food and Nutrition Board needs to consider raising both the Adequate Intake recommendations (how much one should take every day) as well as the Upper Level (the amount one can take on your own, without being under a doctor's care, and without fear of toxicity). My compliments to Dr. Gilchrest.
The "American Decade Rule"
One of the most interesting things I learned in Victoria is that scientists from England, Canada, New Zealand, Australia, and the rest of the world, do not understand the "American Decade Rule." The rule clearly states that if a U.S. scientist and a foreign scientist both discover the same thing in the same decade, the American gets total credit for it, even if the foreigner discovered it first.
Case in point: the discovery of the potent steroid hormone, activated vitamin D or calcitriol—a discovery so important that it regularly starts rumors of a Nobel Prize. Dr. Holick, Dr. Schnoes, and Dr. DeLuca announced their discovery of calcitriol in April of 1971. A group in England, led by Dr. Lawson and Williams, published the same discovery in Nature, in March of 1971, a month earlier. Members of the same English group, Dr. Fraser and Dr. Kodicek, discovered the kidneys make calcitriol in November of 1970, a full six months earlier. However, both English discoveries were within a decade of the Americans. Therefore, the "American Decade Rule" applies and the Americans get total credit. I was surprised that scientists from the Commonwealth find the rule so hard to understand. Holick MF, Schnoes HK, DeLuca HF. Identification of 1,25-dihydroxycholecalciferol, a form of vitamin D3 metabolically active in the intestine. Proc Natl Acad Sci U S A. 1971 Apr;68(4):803–4. Lawson DE, Fraser DR, Kodicek E, Morris HR, Williams DH. Identification of 1,25-dihydroxycholecalciferol, a new kidney hormone controlling calcium metabolism. Nature. 1971 Mar 26;230(5291):228–30. Fraser DR, Kodicek E. Unique biosynthesis by kidney of a biological active vitamin D metabolite. Nature. 1970 Nov 21;228(5273):764–6.
Vitamin D and Neuromuscular Performance
Dr. Heike Bischoff-Ferrari did a wonderful job, not just presenting her data that optimal vitamin D blood levels need to be at least 40 ng/mL, but for presenting Dr. Ed Giovannucci's data (who had to cancel for personal reasons). Dr. Bischoff-Ferrari reminded us that periodontal disease is inversely related to vitamin D blood levels. She also reminded us that there is strong scientific evidence that vitamin D improves neuromuscular performance in older people. She didn't tackle the logical next question: will adequate levels of one of the most potent steroid hormones in the body improve neuromuscular performance in younger people, such as that need for optimal athletic or musical performance? Philip, whose email to me is above, and other readers of this newsletter have been telling me yes.
At Least 5,000 IU Needed Per Day
Dr. Bischoff-Ferrari then presented Dr. Giovannucci's data that one reduces one's risk of all cancers about 17% for every 10 ng/mL of vitamin D in their blood. For cancer of the digestive system, the risk reduction is 43%. His data indicates all Americans should be taking about 2,000 IU per day and some Americans need even more to minimize cancer risk. No one know where the curve flattens out; that is, no one knows how much further cancer reduction one gets from 20, 30, or 40 ng/mL incremental increases in blood levels.
Vitamin D Metabolizing Enzymes
The section on the enzymes that metabolize vitamin D reminded me how much we don't know about vitamin D. Millions of Americans take psychiatric and other medications that interfere with the same system of enzymes, called cytochrome P-450, that metabolize vitamin D. We've known for a long time that some medications taken for epilepsy (Dilantin, phenobarbital, Tegretol) reduce vitamin D blood levels. However, which medications increase levels? I have seen a number of cases of higher than expected levels in patients taking psychiatric medications metabolized by cytochrome P-450 enzymes and some non-psychiatric medications interfere with these same enzymes. This practical area of clinical medicine needs more research.
75% Of Women D-Deficient
Dr. Robert Heaney presented by video hookup and made his quiet but powerful case that about 75% of American women are vitamin D deficient (levels less than 35 ng/mL), that about 3,000 units a day are needed to bring 95% of the population out of the deficient range, and that 10,000 units a day is the safe upper limit. (This does not mean you should take 10,000 units per day, it means scientists should be able to study 10,000 unit daily doses without the bureaucratic difficulty they now encounter).
More Clinical Studies Needed
Dr. Kimball, working with Dr. Reinhold Vieth, presented data that children (age 10–17) only increased their average blood level by 11 ng/mL when given 14,000 units per week for eight weeks and that such dosing was safe. Dr. Vieth is also trying to fill another need in vitamin D clinical science. We need a trial of healthy volunteers taking 20,000 units per day for two or three years. Do blood levels stabilize with oral dosing as they do with sun exposure? Does skin production produce other vitamin D compounds, like dihydrotachysterol, which inhibits the production of calcitriol and thus protects against vitamin D toxicity? Do other vitamin D variants made in the skin induce the metabolism of vitamin D, lower levels, and protect against toxicity? Gray RW, Omdahl JL, Ghazarian JG, DeLuca HF. 25-Hydroxycholecalciferol-1-hydroxylase. Subcellular location and properties. J Biol Chem. 1972 Dec 10;247(23):7528–32.
Does 20,000 units a day for years have any ill effects? Does it affect blood or urine calcium? One study from the 1980s showed 10,000 units a day caused loss in bone density but they used a vitamin D analog (ergocalciferol) which is a xenobiotic (generally foreign to the human body). Therefore, we still don't know what 20,000 units of real vitamin D (cholecalciferol) would do if given for several years.
Dr. Bruce Hollis presented data that reminded us of two overlooked facts: (1) techniques to measure vitamin D in the blood have significant reliability problems, and (2) vitamin D is the only steroid hormone system in the body in which substrate starvation is the rule. That is, only the vitamin D steroid hormone system is chronically short of the substance needed (vitamin D) to fully activate the system. Dr. Reinhold Vieth discussed the second fact in his chapter in Feldman's most recent, and invaluable, textbook: Vitamin D.
Dr. Hollis presented evidence in Victoria that levels of at least 40 ng/mL are required to normalize the enzyme kinetics of vitamin D. [When I say vitamin D blood levels, I'm referring to 25(OH)D levels; Bruce is studying actual vitamin D levels (cholecalciferol) as well as 25(OH)D levels]. Dr. Hollis continues giving pregnant and lactating South Carolina women about 4,000–6,000 units a day in an ongoing study. We predict easier pregnancies and less depression in the moms—lower prenatal and perinatal mortality, fewer birth defects, fewer infections, less diabetes, less psychiatric illness, less asthma, stronger bones, and higher IQs in the children.
Most Of The World Is Deficient
Dr. Paul Lips and Dr. Susan Whiting presented upsetting evidence that vitamin D deficiency is the rule in most of the world; one exception is the Scandinavian countries were vitamin D levels are the highest in Europe, probably due to their cod liver oil. Unfortunately, hip fractures in these same countries are the highest in Europe, probably from the excessive vitamin A in cod liver oil. Stay away from cod liver oil. Johnell O, Gullberg B, Allander E, Kanis JA. The apparent incidence of hip fracture in Europe: a study of national register sources. MEDOS Study Group. Osteoporos Int. 1992 Nov;2(6):298–302.
Upper Limit Needs Revision
Dr. Hathcock did a great job reviewing the evidence that doses below 10,000 units per day have never been shown to be toxic and that 10,000, not 2,000, units per day should be the Upper Limit. He, like so many others, urged the Food and Nutrition Board to revise their outdated recommendations. Moreover, I understand from knowledgeable people at the conference that the Food and Nutrition Board is planning to do just that. Yes!
Higher Blood Levels, Quicker Tan
Dr. Dixon presented fascinating evidence that high vitamin D blood levels prevent sunburn! Of course, it makes sense. When vitamin D levels are low, the skin stays as white as it can to make as much vitamin D as it can, just in case you ignore Dr. Gilchrest's advice. When vitamin D levels are high, the skin rapidly tans to prevent excessive vitamin D skin production. A number of people have emailed me that observation: now that their levels are high, they tan very quickly. I've noticed the same thing.
Athletic Performance and Hair Growth
Dr. Marie Demay presented her basic science research that vitamin D is involved in hair follicles. I loved her talk—although she's a scientist and I'm a psychiatrist so I didn't understand much of what she said. However, I've always thought that vitamin D will really take off once science reveals that it's involved in any of 3 things: sex, athletic performance, or hair growth. In Victoria, we saw evidence for neuromuscular (athletic) performance and hair growth. Two out of three isn't bad; great job, Dr. Demay! In the way of full disclosure, my semi-baldness has not improved on vitamin D, but it has stopped getting worse.
Cancer and Renal Failure
Dr. Cedric Garland recounted how, 26 years ago, he and his brother Frank first thought about the relationship between vitamin D and colon cancer. The brothers, together with colleague Ed Gorham, were the first to provide epidemiological evidence that vitamin D deficiency is involved in numerous cancers. Their seminal 1980 paper is going to be reprinted, a well-deserved honor. Garland CF, Garland FC. Do sunlight and vitamin D reduce the likelihood of colon cancer? Int J Epidemiol. 1980 Sep;9(3):227–31.
Dr. Thadhani and his group from Harvard reviewed their recent discovery that calcitriol and similar drugs increase survival in patients with renal failure. He also presented evidence that renal failure patients have profound deficiencies of both calcitriol and vitamin D and their vitamin D deficiency is not corrected by giving calcitriol or its analogs, which is the current practice.
Vitamin D—A Powerful Antibiotic
Of course, Dr. Robert Modlin stole the show when he reported on his research just published in Science that vitamin D may be, in effect, a powerful antibiotic. For the first time, the UCLA group showed that when researchers add vitamin D to African American blood, their blood makes more of the natural antibiotics that humans rely on to fight infection. Dr. Adrian Martineau, from the Imperial College in London, followed Modlin and showed vitamin D helped fight tuberculosis, probably from increasing these same natural antibiotics. Science has discovered more than 200 of these naturally occurring antimicrobial peptides; they are especially prevalent in the upper and lower respiratory tract; at least one inactivates the influenza virus. Let's not forget that two other groups have also recently shown the antibiotic potential of vitamin D. Liu PT, Stenger S, Li H, Wenzel L, Tan BH, Krutzik SR, Ochoa MT, Schauber J, Wu K, Meinken C, Kamen DL, Wagner M, Bals R, Steinmeyer A, Zügel U, Gallo RL, Eisenberg D, Hewison M, Hollis BW, Adams JS, Bloom BR, Modlin RL. Toll-like receptor triggering of a vitamin D-mediated human antimicrobial response. Science. 2006 Mar 24;311(5768):1770–3. Wang TT, Nestel FP, Bourdeau V, Nagai Y, Wang Q, Liao J, Tavera-Mendoza L, Lin R, Hanrahan JW, Mader S, White JH. Cutting edge: 1,25-dihydroxyvitamin D3 is a direct inducer of antimicrobial peptide gene expression. J Immunol. 2004 Sep 1;173(5):2909–12. Gombart AF, Borregaard N, Koeffler HP. Human cathelicidin antimicrobial peptide (CAMP) gene is a direct target of the vitamin D receptor and is strongly up-regulated in myeloid cells by 1,25-dihydroxyvitamin D3. FASEB J. 2005 Jul;19(9):1067–77. Daher KA, Selsted ME, Lehrer RI. Direct inactivation of viruses by human granulocyte defensins. J Virol. 1986 Dec;60(3):1068–74.
Evidence of A Multitude of Health Benefits
Two hundred and sixteen papers were relegated to poster presentations and all 216 of these scientists thought they should have been chosen to present, as did I. Of course, that would have meant a month-long conference. I only have space to mention of few of the most interesting. Dr. Lu presented evidence that the vitamin D content of fish is much less than previously thought, including mackerel. Salmon is okay but the vitamin D almost disappears when the salmon is fried. Dr. Kimball presented a case series of 12 patients with multiple sclerosis who are now on 40,000 units vitamin D a day with an average blood level of 180 ng/mL (the highest is about 400 ng/mL) and they have no evidence of toxicity or calcium disturbances! (Don't do this on your own; they have a very serious illness, doses were gradually increased, and the patients are being monitored closely.)
Dr. Hardin, from Columbia University, presented evidence that blood levels above 50 ng/mL should help patients with lupus. A group from the University of Manchester presented the mechanism by which vitamin D should reduce arteriosclerosis. A group from the University of Chicago presented evidence that vitamin D should not only prevent colon cancer, but help treat it as well. Dr. Robert Scragg of the University of Auckland presented evidence that ethnic differences in vitamin D levels explain a significant proportion of the reason African Americans are more hypertensive than whites. The group from San Diego presented evidence that vitamin D deficiency is intimately involved in breast, colon, and ovarian cancer.
A group from the University of Manitoba presented evidence that 1-month-old infants tolerate 2,000 units of vitamin a day for three months quite well without any evidence of adverse effects. A group from Wake Forest University demonstrated that higher vitamin D levels were associated with better neuromuscular (athletic) performance in older Americans (should help younger Americans too). A group from the University of Amsterdam showed that the increased risk of falling from vitamin D deficiency is much worse in people with a common genetic variation of the vitamin D receptor. Dr. Chen presented evidence that plain old vitamin D should prevent prostate cancer.
Dr. Barsony, of Georgetown University, presented evidence that low blood sodium is a risk factor for vitamin D deficiency and that such deficiencies may not be able to be corrected until the low blood sodium is corrected. Dr. Barsony really thought "outside the box" to discover this potentially very important clinical finding. Dr. Godar presented evidence that young Americans, not just older Americans, are not getting much vitamin D from sunlight. Dr. Taylor showed evidence that a significant number of young children have a previously undetected form of vitamin D in their blood. (Sunlight triggers the creation of a number of different versions of vitamin D in the skin, that's why it's risky to avoid the sun and only depend on oral vitamin D.) Dr. Patel and a group from the University of Manchester announced evidence that vitamin D deficiency may be involved in inflammatory polyarthritis.
Dr. Grant was involved in six presentations; the most interesting was his replication of a 1937 finding that squamous cell skin cancer reduces one's risk for a number of internal cancers. That's why I used to be so happy when my dermatologist found a squamous cell cancer on my skin. However, now that I maintain my level at about 60 ng/mL, he hasn't been able to find any new ones. Peller S, Stephenson CS. Skin irritation and cancer in the United states Navy. Am J Med Sci: 1937;194:326–333.
Dr. Bulmer and his group from the Royal Victoria Infirmatory produced evidence that vitamin D may play a role in allowing fertilized ova to implant in the uterus and thus enhance fertility. Dr. Reichrath presented evidence that transplant recipients are at a high risk for vitamin D deficiency and that 50,000 units once a month may be the most practical way of ensuring sufficiency. Dr. Selby from the University of Manchester found the same problem in patients with chronic pancreatitis. A group from the University of Tennessee found the same problem in African Americans with heart failure. A group from Norway confirmed that cancer patients do better if they are diagnosed when vitamin D levels are the highest.
Maternal D Deficiency and Brain Damage
Finally, the Australian group headed by Dr. Darryl Eyles and Dr. John McGrath continue to present their convincing evidence (confirmed at this meeting by Dr. Abreu and a group from France) that profound maternal vitamin D deficiency in mammals causes permanent brain damage in their offspring. The racial implication of their work is overwhelming because most of the women in the USA who are profoundly deficient are African American. Are African Americans more likely to be born brain damaged than whites? Would pennies worth of vitamin D improve the disparate prenatal, perinatal, and postnatal outcome in African Americans? The sad fact is that McGrath's and Eyles' work will continue to be ignored because our society has no way to rationally discuss, assimilate, or act on such racially charged scientific discoveries.
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